REVIEW & OUTLOOK
Bullying ImClone
What does the FDA have against saving lives?
In this Enron era, the public spat between ImClone and Bristol-Myers Squibb is playing as one more tale of business greed and deceit. But there's another side to this story, namely that of the patients whose lives remain subject to the untender mercies of the Food and Drug Administration.
ImClone has been a hot Wall Street biotech startup developing the anti-cancer drug Erbitux, its share price hitting a high of $75 late last year. The drug's promise was enough to draw the partnership and cash of the giant Bristol-Myers, but the pair's courtship has soured since December when the FDA refused to act on the Erbitux application. ImClone's stock has fallen to about $17, shareholders are suing, Bristol-Myers is trying to negotiate a better drug-development deal, and the press and politicians are all clucking again about business mores.
Erbitux is what's known as an "epidermal growth factor inhibitor," a new class of cancer drugs that aim to disrupt the biochemical signals that turn healthy cells into malignant ones. Based on animal studies, ImClone concluded that Erbitux would probably work best by preventing those cancer cells not killed by traditional chemotherapy from reactivating the tumor. So ImClone appears to have done the ethical thing by giving patients in its study the best chance of survival.
To wit, it tested Erbitux against colon cancer in combination with a traditional chemical agent, irinotecan, in patients who had not responded to irinotecan alone. ImClone reported that 22.5% of 121 trial patients responding to treatment, a high rate for a cancer drug. Its trial was overseen by Dr. Leonard Saltz of Memorial Sloan-Kettering Cancer Center in New York, after whom the world's standard chemo regimen for colon cancer is named.
But the FDA was not impressed, declining even to look at ImClone's application. In documents leaked to the press, the agency said ImClone hadn't provided enough information to prove that Erbitux, and not irinotecan, had produced the positive results. The FDA suggested further time-consuming trials could be needed, perhaps involving Erbitux alone--a demand that raises alarm bells among doctors since many drugs are expressly designed to work in combination.
In any event, we aren't talking about treating allergies; these are cancer patients, some of whom have already failed existing treatments. Perfect science might demand another 120 cancer patients be tested against a placebo, which means pretending to give them something that saves their lives but in fact doesn't. But this is hardly consistent with the Hippocratic injunction to "do no harm."
The FDA seems to be using ImClone to send a signal that it's going to demand rigorous proof of a drug's "effectiveness," even in cases of terminal illness. Proving safety is relatively quick and easy. And just about everyone agrees biological agents like Erbitux are orders of magnitude safer than traditional chemotherapy drugs, which poison the whole body in an attempt to kill a few cancer cells.
But it is "effectiveness" that takes drug companies a decade and an average $800 million to prove. And if effectiveness is already proving a troublesome barrier with drugs like Erbitux, it will be all the more so as biotechnology allows doctors to design treatments tailored to an individual's genetic code, where large randomized trials will be, by definition, impossible. But rather than adapt to these new realities, the FDA seems to want even more stringent effectiveness tests.
This is precisely when a new FDA commissioner should be exerting leadership over this keep-our-power bureaucracy. But President Bush has yet to name one, and the lead candidate is someone who seems to want more FDA control in any case. Neither this White House nor HHS Secretary Tommy Thompson have shown the foggiest understanding of the issues at stake in drug approvals and regulation. The ImClone fiasco is a wake-up call.
